Synthesis of sialylated human milk oligosaccharides by automated glycan assembly

Abstract Sialic acids cap the ends of many glycan chains and play pivotal roles in cell signaling, immunity, and pathogen interactions. However, the fast synthesis of sialylated glycans by automated glycan assembly (AGA) has remained a long-standing challenge. Here we show a general strategy that leverages macrobicyclic sialic acid building blocks to achieve reliable α(2,3)- and α(2,6)-sialylation on solid support. Using this method, a collection of nine sialylated human milk oligosaccharides (H